BACKGROUND/ PURPOSE: Clinical application of gene therapy for patients who have inflammatory bowel disease or short bowel syndrome will require the development of new strategies to improve the efficiency of small intestinal gene transfer. Previously, the authors developed a method for adenoviral-mediated small intestinal gene transfer in vivo in neonatal and adult mice. The present study evaluates the hypothesis that the integrins alpha(v)beta3 and alpha(v)beta5, the secondary receptors for adenoviral internalization, play a facilitative role in neonatal murine adenoviral-mediated small intestinal gene transfer. METHODS: Immunohistochemical techniques identified the integrin alpha(v)beta3 and the integrin subcomponents alpha(v), beta3, and beta5 in neonatal and adult small intestine. The effects of integrin receptor antagonists on transgene expression was also studied in our neonatal model of adenoviral-mediated small intestinal gene transfer in vivo. RESULTS: Gene transfer was significantly decreased by the addition of integrin receptor antagonists versus control peptide. Integrin alpha(v)beta3 and integrin subcomponent alpha(v), beta3, and beta5 are expressed in neonatal and adult small intestine. Integrin antagonists administered simultaneously blocked efficient adenoviral-mediated neonatal small intestinal gene transfer in vivo compared with control peptide. CONCLUSION: Strategies to upregulate integrin expression may improve adenoviral-mediated small intestinal gene transfer.
BACKGROUND/ PURPOSE: Clinical application of gene therapy for patients who have inflammatory bowel disease or short bowel syndrome will require the development of new strategies to improve the efficiency of small intestinal gene transfer. Previously, the authors developed a method for adenoviral-mediated small intestinal gene transfer in vivo in neonatal and adult mice. The present study evaluates the hypothesis that the integrins alpha(v)beta3 and alpha(v)beta5, the secondary receptors for adenoviral internalization, play a facilitative role in neonatal murine adenoviral-mediated small intestinal gene transfer. METHODS: Immunohistochemical techniques identified the integrin alpha(v)beta3 and the integrin subcomponents alpha(v), beta3, and beta5 in neonatal and adult small intestine. The effects of integrin receptor antagonists on transgene expression was also studied in our neonatal model of adenoviral-mediated small intestinal gene transfer in vivo. RESULTS: Gene transfer was significantly decreased by the addition of integrin receptor antagonists versus control peptide. Integrin alpha(v)beta3 and integrin subcomponent alpha(v), beta3, and beta5 are expressed in neonatal and adult small intestine. Integrin antagonists administered simultaneously blocked efficient adenoviral-mediated neonatal small intestinal gene transfer in vivo compared with control peptide. CONCLUSION: Strategies to upregulate integrin expression may improve adenoviral-mediated small intestinal gene transfer.
Authors: Julien Revaud; Yves Unterfinger; Nicolas Rol; Muhammad Suleman; Julia Shaw; Sandra Galea; Françoise Gavard; Sandrine A Lacour; Muriel Coulpier; Nicolas Versillé; Menzo Havenga; Bernard Klonjkowski; Gina Zanella; Stéphane Biacchesi; Nathalie Cordonnier; Blaise Corthésy; Juliette Ben Arous; Jennifer P Richardson Journal: Front Cell Infect Microbiol Date: 2018-01-25 Impact factor: 5.293